The goals of this research are to develop advanced magnetic resonance spectroscopy (MRS) and imaging techniques and to apply them and other complementary methods to studying brain metabolism, neurotransmission and enzyme activity. MRS allows measurement of neurotransmission of glutamate and GABA in vivo, which play important roles in many major psychiatric diseases including depression and schizophrenia. During 2010-2011, significant progress has been made in the development and applications of novel spectroscopic techniques for studying metabolism and neurotransmission in vivo in the brain. From our previous work, we have found that 13C labeling of glutamate and glutamine can be measured from human subjects by low power proton stochastic decoupling in the carboxylic/amide spectral region (Li, et al, NMR Biomed, 2010). Since then, we have devised a novel windowed stochastic decoupling technique that allows for a 50% additional reduction in radiofrequency power deposition into the brain, making it feasible to perform 13C MRS at very high magnetic field strength (Yang et al, J. Magn Reson Imaging, in press). We have also validated that the carboxylic/amide 13C isotopomers can be used for simultaneous detection of the metabolic action of two different substrates (Yang et al, J Neurosci Methods, 2011). A novel 13C homonuclear spectral editing method has been developed to spectrally resolve glutamine from overlapping aspartate. Using our GABA method, Marenco et al found that anterior cingulate cortex GABA concentration is modulated by GAD1 and COMT (Marenco et al, Neuropsychopharmacology, 2010). A significant association of GABA level with ErbB4 was identified recently (Marenco et al, J. Neurosci, 2011). In addition, collaborations with Dr. Gregor Hasler have led to novel findings of genetic effects on variations in MRS measures of N-acetylaspartate and GABA (BDNF bipolar disorder risk allele on prefrontal N-acetylaspartate and TPH2 panic disorder risk allele on GABA). By introducing numerical regularization methods into MRS we have also succeeded in quantifying N-acetylaspartyl glutamate (Zhang et al, Magn Reson Med, 2011). Finally, we proposed and tested a novel method for extracting MRS signals from irregularly shaped region of interest using the sensitivity heterogeneity of multichannel phased array receive coils (An et al, Magn Reson Med, 2011).